Controlled release of peptides and proteins from biodegradable polyester microspheres: an approach for treating infectious diseases and malignancies

Abstract

An approach to enhance the immunogenicity of peptide-based vaccines for malaria and the immunoregulatory activity of recombinant human interleukin-1α (IL-1) is described. The approach involves the encapsulation of these molecules in, and their controlled release from, biodegradable polyester microspheres of lactic and glycolic acids (PLGA). The microspheres are prepared by the modified solvent evaporation method based on a double emulsion. Two types of microspheres composed of PLGA (75:25 lactic/glycolic acid) and of different MW were constructed for each molecule. The release characteristics of these molecules from these microspheres were evaluated using spectroscopy and bioactivity assays. In vivo studies established the feasibility of PLGA carriers as an immunization vehicle for malaria peptide-based vaccines; the induced immune responses in mice were stronger than those obtained with peptide in complete Freund's adjuvant. In addition, these studies provide preliminary evidence that PLGA microspheres with encapsulated IL-1 can be used as a new strategy for the efficient delivery of this cytokine to tumor sites in immunotherapy.